Skip to main content
NCBI home page
BMJ Clinical Evidence logoLink to BMJ Clinical Evidence
. 2015 May 13;2015:0705.

Uveitis (acute anterior)

Niaz Islam 1,#, Carlos Pavesio 2,#
PMCID: PMC4429848

Abstract

Introduction

Anterior uveitis is rare, with an annual incidence of 12 per 100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors such as high frequency of HLA-B27 in the population. It is often self-limiting but can, in some cases, lead to complications such as posterior synechiae, cataract, glaucoma, cystoid macular oedema, and chronic uveitis.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions on acute anterior uveitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 10 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids (topical/eye drops, oral, subconjunctival injection), mydriatics, and non-steroidal anti-inflammatory drug eye drops.

Key Points

Anterior uveitis is inflammation of the uveal tract, and includes iritis (inflammation of the iris) and iridocyclitis (inflammation of both iris and ciliary body).

  • It is usually rare, with an annual incidence of 12 per 100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors such as high frequency of HLA-B27 in the population.

  • It is often self-limiting but can in some cases lead to complications such as posterior synechiae, cataract, glaucoma, cystoid macular oedema, and chronic uveitis.

This review searched for RCTs examining the effects of the listed interventions. In fact, we found few such studies to inform clinical practice. There is a need for further high-quality RCTs in this field.

Corticosteroid eye drops have been the standard treatment for uveitis since the early 1950s, although RCT evidence supporting their effectiveness is somewhat sparse.

  • Widely known adverse effects of topical corticosteroid eye drops include local irritation, hyperaemia, raised intraocular pressure (steroid responder), and blurred vision.

  • We found seven RCTs comparing different corticosteroid eye drops versus each other. Overall, RCTs were small and evidence was limited, and we were unable to draw robust conclusions.

  • We found no RCTs on the effects of oral corticosteroids or subconjunctival corticosteroid injections.

The studies examining the effects of NSAID eye drops were either too small or of insufficient quality to allow us to judge their effectiveness in treating anterior uveitis.

We found no RCTs on the effects of mydriatics.

Clinical context

General background

Anterior uveitis is inflammation of the uveal tract, and includes iritis (inflammation of the iris) and iridocyclitis (inflammation of both iris and ciliary body). It is rare, with an annual incidence of 12 per 100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors such as high frequency of HLA-B27 in the population. It is often self-limiting but can, in some cases, lead to complications such as posterior synechiae, cataract, glaucoma, cystoid macular oedema, and chronic uveitis. Corticosteroid eye drops, non-steroidal anti-inflammatory (NSAID) drops, tablets, and periocular corticosteroid injections with mydriatics are treatment options.

Focus of the review

Corticosteroid eye drops have been the standard treatment for uveitis since the early 1950s. NSAID drops, tablets, and periocular steroid injections with mydriatics have also been reported as treatment options. An updated literature search was, therefore, carried out to investigate the effectiveness of treatments.

Comments on evidence

Three additional RCTs on the effects of corticosteroid eye drops versus each other have been identified and added to this updated review. Overall, we have included eight RCTs on the effects of corticosteroids and three RCTs on NSAID drops. We found no systematic reviews or RCTs comparing different mydriatic drugs or different potencies of mydriatic drugs.

Search and appraisal summary

The update literature search for this review was carried out from the date of the last search, November 2009, to August 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 130 studies. After deduplication and removal of conference abstracts, 81 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 67 studies and the further review of 14 full publications. Of the 14 full articles evaluated, three RCTs were added at this update.

Additional information

Widely known adverse effects of topical corticosteroid eye drops include raised intraocular pressure ('steroid responder') among others. Harms data need to be considered, with the consequences of placebo or no treatment leading to the possibility of developing sight loss by secondary cystoid macular oedema.

About this condition

Definition

Anterior uveitis is inflammation of the uveal tract, and includes iritis and iridocyclitis. It can be classified according to its clinical course into acute or chronic anterior uveitis or according to its clinical appearance into granulomatous or non-granulomatous anterior uveitis. Acute anterior uveitis is characterised by an extremely painful red eye, often associated with photophobia, and occasionally with decreased visual acuity. Chronic anterior uveitis is defined as inflammation lasting more than 6 weeks. It is usually asymptomatic but many people have mild symptoms during exacerbations.

Incidence/ Prevalence

Acute anterior uveitis is rare, with an annual incidence of 12 per 100,000 population. It is particularly common in Finland (annual incidence 22.6/100,000 population, prevalence 68.7/100,000 population), probably because of genetic factors such as the high frequency of HLA-B27 in the Finnish population. It is equally common in men and women, and more than 90% of cases occur in people older than 20 years of age.

Aetiology/ Risk factors

No cause is identified in 60% to 80% of people with acute anterior uveitis. This most common category is also termed 'idiopathic anterior uveitis'. Systemic disorders that may be associated with acute anterior uveitis include ankylosing spondylitis, Reiter's syndrome, Kawasaki's disease, infectious uveitis, Behçet's syndrome, inflammatory bowel disease, interstitial nephritis, sarcoidosis, Vogt-Koyanagi-Harada syndrome, and masquerade syndromes. Acute anterior uveitis also occurs in association with HLA-B27 expression not linked to any systemic disease. Acute anterior uveitis may occur after surgery, or as an adverse drug or hypersensitivity reaction.

Prognosis

Acute anterior uveitis is often self-limiting, but we found no evidence about how often it resolves spontaneously, in which people, or over what length of time. Complications include posterior synechiae, cataract, glaucoma, cystoid macular oedema, and chronic uveitis. In a study of 154 people (232 eyes) with acute anterior uveitis (119 people HLA-B27 positive), visual acuity was better than 20/60 in 209/232 eyes (90%), and 20/60 or worse in 23/232 (10%) eyes, including worse than 20/200 (classified as legally blind) in 11/232 (5%) eyes.

Aims of intervention

To reduce inflammation; to relieve pain; and to prevent complications and loss of visual acuity, with minimal adverse effects.

Outcomes

Disease severity degree of inflammation using scores that register a range of different variables as markers of disease severity (number of anterior chamber cells per examination field, flare in the anterior chamber, keratic precipitates, ciliary flush, and severity of symptoms [photophobia and pain]); quality of life; adverse effects.

Methods

BMJ Clinical Evidence search and appraisal August 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to August 2014, Embase 1980 to August 2014, and The Cochrane Database of Systematic Reviews 2014, issue 8 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing 20 or more individuals (10 in each arm), of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. All serious adverse effects, or those adverse effects that are reported as statistically significant, will be data extracted for inclusion in the harms table of the review. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the BMJ Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table 1.

GRADE evaluation of interventions for acute anterior uveitis

Important outcomes Disease severity, adverse effects
Number of studies (participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of interventions on acute anterior uveitis?
1 (60) Disease severity Corticosteroid eye drops v placebo eye drops 4 –3 0 0 0 Very low Quality points deducted for sparse data, incomplete reporting of results, poor follow-up, and no intention-to-treat analysis
7 (791) Disease severity Corticosteroid eye drops v each other 4 –2 0 –1 0 Very low Quality points deducted for weak methods and incomplete reporting of results; directness point deducted for use of concomitant medication, which may have affected some outcomes
1 (111) Quality of life Corticosteroid eye drops v each other 4 –2 0 –1 0 Very low Quality points deducted for sparse data and weak methods (participants not blinded); directness point deducted for use of concomitant medication
1 (64) Disease severity NSAID eye drops v placebo eye drops 4 –2 0 –2 0 Very low Quality points deducted for sparse data and no intention-to-treat analysis; directness points deducted for unclear outcome (clinical cure) and co-intervention (atropine)
3 (173) Disease severity NSAID eye drops v corticosteroid eye drops 4 –2 0 –2 0 Very low Quality points deducted for sparse data and no intention-to-treat analysis; directness points deducted for unclear outcome (clinical cure) and co-intervention (atropine)
Open in a new tab

Type of evidence: 4 = RCT. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

Iridocyclitis

Inflammation of both iris and ciliary body. Cells are present in the anterior chamber and in the vitreous.

Iritis

Inflammation of the iris. Cells are seen in the anterior chamber but not in the vitreous.

Masquerade syndromes

Comprise a group of disorders that occur with intraocular inflammation and are often misdiagnosed as a chronic idiopathic uveitis.

Posterior synechiae

Adhesions between the iris and the lens capsule.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Niaz Islam, Moorfields Eye Hospital, London, UK.

Carlos Pavesio, Moorfields Eye Hospital, London, UK.

References

  • 1.Smith RE, Nozik RA, eds. Uveitis: a clinical approach to diagnosis and management. 2nd ed. Baltimore: Williams & Wilkins, 1989. [Google Scholar]
  • 2.Darrel RW, Wagner HP, Kurland CT. Epidemiology of uveitis: incidence and prevalence in a small urban community. Arch Ophthalmol 1962;68:501–514. [DOI] [PubMed] [Google Scholar]
  • 3.Päivönsalo-Hietanen T, Tuominen J, Vaahtoranta-Lehtonen H, et al. Incidence and prevalence of different uveitis entities in Finland. Acta Ophthalmol Scand 1997;75:76–81. [DOI] [PubMed] [Google Scholar]
  • 4.Rosenbaum JT. Uveitis. An internist's view. Arch Intern Med 1989;149:1173–1176. [DOI] [PubMed] [Google Scholar]
  • 5.Nussenblatt RB, Whitcup SM, eds. Uveitis: fundamentals and clinical practice. Third ed. St Louis, MO: Mosby, 2003. [Google Scholar]
  • 6.Linssen A, Meenken C. Outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis. Am J Ophthalmol 1995;120:351–361. [DOI] [PubMed] [Google Scholar]
  • 7.Dunne JA, Travers JP. Topical steroids in anterior uveitis. Trans Ophthalmol Soc UK 1979;99:481–484. [PubMed] [Google Scholar]
  • 8.Foster CS, Alter G, DeBarge RL, et al. Efficacy and safety of rimexolone 1% ophthalmic suspension vs prednisolone acetate in the treatment of uveitis. Am J Ophthalmol 1996;122:171–182. [DOI] [PubMed] [Google Scholar]
  • 9.The Loteprednol Etabonate US Uveitis Study Group. Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Am J Ophthalmol 1999;127:537–544. [DOI] [PubMed] [Google Scholar]
  • 10.Hedayatfar A, Hashemi H, Asgari S, et al. Comparison of efficacy and ocular surface toxicity of topical preservative-free methylprednisolone and preserved prednisolone in the treatment of acute anterior uveitis. Cornea 2014;33:366–372. [DOI] [PubMed] [Google Scholar]
  • 11.Sheppard JD, Toyos MM, Kempen JH, et al. Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study. Invest Ophthalmol Vis Sci 2014;55:2993–3002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Foster CS, Davanzo R, Flynn TE, et al. Durezol (difluprednate ophthalmic emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther 2010;26:475–483. [DOI] [PubMed] [Google Scholar]
  • 13.Young BJ, Cunninghan WF, Akingbehin T. Double-masked controlled clinical trial of 5% tolmetin versus 0.5% prednisolone versus 0.9% saline in acute endogenous nongranulomatous anterior uveitis. Br J Ophthalmol 1982;66:389–391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Dunne JA, Jacobs N, Morrison A, et al. Efficacy in anterior uveitis of two known steroids and topical tolmetin. Br J Ophthalmol 1985;69:120–125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Sand BB, Krogh E. Topical indometacin, a prostaglandin inhibitor, in acute anterior uveitis. A controlled clinical trial of non-steroid versus steroid anti-inflammatory treatment. Acta Ophthalmol (Copenh) 1991;69:145–148. [DOI] [PubMed] [Google Scholar]
BMJ Clin Evid. 2015 May 13;2015:0705.

Corticosteroids

Summary

DISEASE SEVERITY Corticosteroid eye drops compared with placebo eye drops: We don't know whether corticosteroid eye drops are more effective than placebo eye drops at reducing symptom severity at 14–21 days in people with acute anterior uveitis, as we found insufficient evidence from one small RCT ( very low-quality evidence ). Corticosteroid eye drops compared with each other: We don’t know whether any one corticosteroid eye drop is consistently more effective than other corticosteroid eye drops in people with acute anterior uveitis, as we found insufficient evidence from mainly small limited RCTs (very low-quality evidence). Corticosteroid eye drops compared with non-steroidal anti-inflammatory drug (NSAID) eye drops: We don't know whether corticosteroid eye drops are more effective then NSAID eye drops at increasing clinical cure rates (not further defined) at 14–21 days in people with acute anterior uveitis, some of whom were also receiving atropine eye drops (very low-quality evidence). QUALITY OF LIFE Corticosteroid eye drops compared with each other: We don’t know whether difluprednate eye drops and prednisolone acetate eye drops differ in effectiveness at improving quality of life scores (measured by NEI visual function questionnaire VFQ-25) at day 42 in people with acute anterior uveitis, as we found insufficient evidence from one small RCT (very low-quality evidence). NOTE Topical corticosteroids have been standard treatment for anterior uveitis since the early 1950s, especially for people with acute or severe uveitis. Placebo-controlled RCTs are unlikely to be conducted. We found no direct information from RCTs about oral or subconjunctivally injected corticosteroids in the treatment of people with acute anterior uveitis.

Benefits

Corticosteroid eye drops versus placebo eye drops:

We found one RCT (60 people), which compared three treatments: betamethasone phosphate 0.1% (2 drops every 2 hours), clobetasone butyrate 0.1% (2 drops every 2 hours), and placebo. The RCT found no significant difference with corticosteroid (betamethasone phosphate/clobetasone butyrate) compared with placebo eye drops in symptom severity after 14 or 21 days (results presented graphically; see Comment section).

Corticosteroid eye drops versus each other:

We found seven RCTs reported in five reviews.

We found two papers reporting four RCTs. Two RCTs compared prednisolone 1% eye drops with rimexolone 1% eye drops. The larger RCT (183 people) found no significant difference in the number of anterior chamber cells per examination field after 28 days (see Comment; 0.4 cells/examination field with rimexolone v 0.2 cells/examination field with prednisolone, difference 0.2 cells/examination field, CI not reported; P = 0.16). The smaller RCT (83 people) also found no significant difference in the number of anterior chamber cells per examination field after 28 days (see Comment ; 0.3 cells/examination field with rimexolone v 0.2 cells/examination field with prednisolone; difference 0.1 cells/examination field; CI not reported; P = 0.40). Two RCTs compared prednisolone 1% with loteprednol 0.5% eye drops. The larger RCT (175 people) found that prednisolone significantly increased the proportion of people with fewer than five anterior chamber cells per examination field after 28 days compared with loteprednol (5 people lost to follow-up; 77/89 [87%] with prednisolone v 58/81 [72%] with loteprednol; RR 1.20, 95% CI 1.03 to 1.42; NNT 7, 95% CI 4 to 35). The smaller RCT (70 people) found that more people had fewer than five anterior chamber cells per examination field with prednisolone compared with loteprednol, but the difference was not significant (see Comment).

The fifth RCT (74 people, 78 eyes, 16 years or older, at least 2+ anterior chamber cells) compared non-preserved methylprednisolone sodium succinate 1% with preserved prednisolone acetate suspension 1% eye drops followed by a 2-week tapering regimen. It randomised by eyes rather than by people. The preserved prednisolone was a commercially available preparation, while the methylprednisolone preparation was prepared at the participating hospital. All participants also received homatropine. At 1 week, if people had not improved clinically (two-step reduction of anterior cell grade), an additional regional corticosteroid injection or oral prednisolone was given. It also reported that those considered refractory were then treated with preserved prednisolone drops for the rest of the study. It found no significant difference between groups in anterior chamber cell grade improvement or anterior chamber flare at day 14 (mean anterior chamber cell grade improvement [SUN classification]: 2.52 with methylprednisolone v 2.86 with prednisolone, P = 0.092; reduction in anterior chamber flare: 188.4 with methylprednisolone v 240.1 with prednisolone, P = 0.141; absolute numbers not reported, see Comment). The RCT reported no significant difference between groups in the percentage of people with reduced inflammation (grade 1 or less) at 14 days (29/38 [76.3%] with methylprednisolone v 24/34 [70.6%] with prednisolone, P = 0.582).

The sixth double-blind RCT (111 people, age 4–87 years) compared difluprednate 0.05% with prednisolone acetate 1.00% at 21 sites in the US. Treatment was given for 14 days, with people tapered off medication over day 14 to day 27. People with increased intra-ocular pressure were allowed a lowering agent at physician discretion, and the use of concomitant mydriatic or cycloplegic drops was also permitted at investigator discretion. The RCT reported an ITT (110 people) and per-protocol (93 people) analysis. We have reported the ITT analysis where possible. The RCT found no significant difference between groups in change in anterior cell grade at day 14 (110 people; mean decrease, grade 0 = 1 cell or less to grade 4 = 50 or above: 2.1 with difluprednate v 1.9 with prednisolone acetate, P = 0.29). It reported that the proportion of people whose anterior chambers were completely clear was comparable at most study visits (93 people, results presented graphically, day 0 to 42, P at least 0.18) except at day 3 (P = 0.046) and day 21 (P = 0.013), which favoured difluprednate. It found no significant difference between groups in total symptom scores at day 42 (93 people, mean change from baseline measured by VAS [including eye pain, photophobia, blurred vision, lacrimation]: –146.2 with difluprednate v –155.5 with prednisolone acetate, P = 0.71). It found no significant difference between groups in quality of life scores at 42 days (mean improvement in NEI VFQ-25 composite score, scale 0 to 100: 7.8 with difluprednate v 5.5 with prednisolone acetate, P = 0.671).

The seventh double-blind RCT (90 people, mean age 43–46 years, >10 anterior chamber cells and a flare score of 2 or greater in the same eye) compared difluprednate ophthalmic solution 0.05% with prednisolone acetate ophthalmic suspension 1% for 14 days, followed by a 2-week tapering regimen at 22 sites in the US. People with increased intraocular pressure were allowed a lowering agent at physician discretion, and concomitant mydriatic or cycloplegic drops were permitted. The RCT reported 'similar' between-group change in anterior chamber cell grade at 14 days (87 people; mean anterior cell grade improvement, grade 0 = 1 cell or less to grade 4 =  0 cells or above: 2.1 with difluprednate v 1.9 with prednisolone, P value not reported). It found no significant difference between groups in the proportion of people in whom the anterior chambers were clear at 14 days (87 people, grade 0 = 1 cell or less: 69% with difluprednate v 62% with prednisolone, reported as not significant, P value not reported). The RCT did not report a between-group analysis for total symptom scores or for total quality of life measures (NEI VFQ-39 and WLQ), so we have not reported these data further.

Corticosteroid eye drops versus NSAID eye drops:

See Benefits of topical NSAID eye drops.

Oral corticosteroids versus placebo or topical NSAIDs or mydriatics:

We found no systematic review or RCTs.

Subconjunctival corticosteroid injection versus placebo or topical NSAIDs or mydriatics:

We found no systematic review or RCTs.

Harms

Corticosteroid eye drops:

Widely known adverse effects of topical corticosteroid eye drops include local irritation, hyperaemia, oedema, and blurred vision. Topical eye drops have been associated with an increase in intraocular pressure within 3 to 6 weeks of the start of treatment in susceptible people ('steroid responder'), and more prolonged use may lead to the formation of posterior subcapsular cataracts. Another potential effect is increased risk of herpes simplex keratitis.

Corticosteroid eye drops versus placebo:

The RCT did not report on harms.

Corticosteroid eye drops versus each other:

In the four RCTs included in two reports, adverse events were generally mild, resolved without treatment, and did not result in permanent damage.

In the smaller RCT comparing loteprednol with prednisolone eye drops, 4/70 (6%) people were withdrawn because of adverse effects (cystoid macular oedema and ocular symptoms in the loteprednol group, and interstitial keratitis and increased age-related macular degeneration in the prednisolone group).The largest RCTs found clinically relevant increases in intraocular pressure (defined as >10 mm Hg from baseline) more frequently with prednisolone compared with rimexolone, and with prednisolone compared with loteprednol, although the differences were not significant (11/94 [12%] people with prednisolone v 6/89 [7%] people with rimexolone; RR 1.7, 95% CI 0.7 to 4.5; 6/91 [7%] people with prednisolone v 1/84 [1%] people with loteprednol; RR 5.5, 95% CI 0.7 to 45.0).

The fifth RCT reported that there was no significant difference between groups in intraocular pressure at 1 to 2 weeks follow-up (results presented graphically, P value not reported).

The sixth RCT reported that 25 people (45%) with difluprednate and 19 people (35%) with prednisolone reported adverse effects (P value not reported). It reported that the majority of adverse effects (76 in total) were ocular-related and mild in intensity. Eight adverse effects were deemed to be treatment related: two cases of mild punctuate keratitis with difluprednate, and six cases of elevated IOP (5 mild cases with difluprednate and 1 moderate case with prednisolone). Two people discontinued treatment in the difluprednate group due to adverse effects, and one person in the prednisolone group. Two serious adverse effects occurred in the difluprednate group (necrotising retinitis and moderate systemic hypertension), but neither event was assessed as related to the study drug. Intraocular pressure increase 21 mmHg or greater, and with a change 10 mmHg or greater above baseline at the same visit, occurred in nine people (16%) with difluprednate compared with six people (11%) with prednisolone (reported as P at least 0.15 at all time points).

The seventh RCT reported that 70% of people with prednisolone acetate and 68% of people with difluprednate reported adverse effects (P value not reported). These were described as mostly ocular and mild or moderate in intensity. Five people withdrew from the study due to adverse effects associated with worsening uveitis symptoms (5 with prednisolone acetate v 0 with difluprednate, P = 0.01). Ocular adverse effects thought to be treatment related occurred in 20 (40%) people with difluprednate versus 12 (30%) of people with prednisolone (P value not reported). These included punctuate keratitis (16% of people with difluprednate v 13% of people with prednisolone), eye pain (4% v 0%), vision blurred (8% v 0%), eye irritation (10% v 3%), dry eye (6% v 0%), IOP increase (12% v 5%), and clinically significant IOP increase (6% v 5%; P values for comparison of individual adverse effects not reported).

Corticosteroid eye drops versus NSAID eye drops:

See Harms of topical NSAID eye drops.

Oral corticosteroids versus placebo or topical NSAIDs or mydriatics:

We found no RCTs.

Subconjunctival corticosteroid injection versus placebo or topical NSAIDs or mydriatics:

We found no RCTs.

Comment

Topical corticosteroids have been standard treatment for anterior uveitis since the early 1950s, especially for people with acute or severe uveitis.

Corticosteroid eye drops versus placebo eye drops:

In the RCT comparing corticosteroid eye drops with placebo, 12/60 (20%) people did not complete the trial, and analysis of data was not by intention to treat. Of these, 4/12 (33%) people were withdrawn from the placebo group because of the severity of their anterior uveitis. These withdrawn participants from the placebo group were treated with topical corticosteroids. Nevertheless, the trial was too small to detect any clinically important effect of topical corticosteroids. No RCTs were found comparing corticosteroid eye drops with combined NSAIDs and mydriatics.

Corticosteroid eye drops versus each other:

In the RCTs comparing prednisolone with rimexolone, people were excluded from analysis for a variety of reasons (23/183 [13%] in the larger RCT and 8/93 [9%] in the smaller RCT). The smaller RCT comparing prednisolone with loteprednol enrolled people in the US and the UK; however, it only reported results for the subgroup of people recruited from the US, making the results difficult to interpret.

The fifth RCT was conducted in a single centre in Tehran, and all measurements were made by one person. Investigators were blinded, but participants were not. Of 74 people randomised, two people (3%) did not complete the study due to protocol violation or loss to follow-up. In addition, at the first-week follow-up, 13/72 (18%) people were withdrawn because the investigator deemed that they were refractory to treatment, and they received additional corticosteroid injection or oral corticosteroid and were switched to preserved prednisolone drops. It was unclear whether these people were included in the analysis of anterior cell count or flare. All participants received homatropine eye drops.

In the sixth RCT, funding for the study was provided by a pharmaceutical company, and four out of the five authors had served as consultants for the company, while the fifth was an employee of the company. It did not report on the use of concomitant mydriatic or cycloplegic drops (which were allowed), or whether their use differed between groups.

The seventh RCT, which also allowed concomitant medication, noted that the use of mydratic or cycloplegic agents could have affected outcomes such as pain and overall symptoms if their use varied between groups. It reported that mydratic or cycloplegic agents were used in 36% of people with difluprednate compared with 20% with prednisolone (P value not reported). Funding for the RCT was supplied by a pharmaceutical company, two authors were former employees of the company and current shareholders at the time of the trial, and two authors had consulting agreements with the company. One author was common to both the sixth and the seventh RCT.

Clinical guide

Generally, topical corticosteroid eye drops are tapered down and stopped. People who require long-term maintenance daily corticosteroid eye drops, to prevent relapse or cystoid macular oedema, require a minimum yearly intraocular pressure check in order to identify late intraocular pressure rise or steroid-induced glaucoma.

Substantive changes

Corticosteroids Three RCTs added. Categorisation unchanged (likely to be beneficial).

BMJ Clin Evid. 2015 May 13;2015:0705.

Non-steroidal anti-inflammatory (NSAID) eye drops

Summary

DISEASE SEVERITY NSAID eye drops compared with placebo: We don't know whether NSAID eye drops (tolmetin) are more effective than placebo at increasing cure rates (not further defined) at 21 days in people with acute anterior uveitis who were also receiving atropine eye drops ( very low-quality evidence ). NSAID eye drops compared with corticosteroid eye drops: We don't know whether NSAID eye drops are more effective than corticosteroid eye drops at increasing clinical cure rates (not further defined) at 14–21 days in people with acute anterior uveitis, some of whom were also receiving atropine eye drops (very low-quality evidence).

Benefits

NSAID eye drops versus placebo eye drops:

We found one RCT (100 people) that compared three types of eye drops: NSAID (tolmetin 5.0%), corticosteroid (prednisolone 0.5%), and placebo (sterile saline 0.9%). People were asked to instill two drops every 2 hours during waking hours plus atropine 1% eye drops once daily. The RCT found no significant difference between NSAID eye drops and placebo eye drops in clinical cure rate after 21 days (15/32 [47%] with tolmetin v 16/32 [50%] with placebo; RR 0.9, 95% CI 0.6 to 1.6).

NSAID eye drops versus corticosteroid eye drops:

We found three RCTs. The first RCT (described above) found no significant difference between NSAID eye drops and corticosteroid eye drops in clinical cure rate after 21 days (see Comment; 15/32 [47%] with tolmetin v 22/32 [69%] with prednisolone; RR 0.7, 95% CI 0.4 to 1.1). The second RCT (71 people) compared three treatments: prednisolone disodium phosphate 0.5%, betamethasone disodium phosphate 0.1%, and tolmetin sodium dihydrate 5.0%. People were asked to instill one drop every 2 hours during waking hours, and all received atropine 1% eye drops once daily. The RCT found no significant difference between the NSAID (tolmetin sodium dihydrate) eye drops and corticosteroid (prednisolone disodium phosphate/betamethasone disodium phosphate) eye drops in clinical cure rate after 21 days (see Comment; 12/21 [57%] people with tolmetin sodium dihydrate v 31/39 [79%] with prednisolone disodium phosphate/betamethasone disodium phosphate; RR 1.4, 95% CI 0.9 to 2.1). The third RCT (49 people) compared NSAID eye drops (indometacin [indomethacin] 0.1%) with corticosteroid (dexamethasone 1.0%) eye drops given six times daily. Most people (equal numbers in each group) also received atropine eye drops three times daily. The RCT found a lower proportion of people clinically cured after 14 days with indometacin, but the difference was of borderline significance (see Comment; 12/25 [48%] people with indometacin v 18/24 [75%] people with dexamethasone; RR 0.6, 95% CI 0.4 to 1.0).

Harms

NSAID eye drops versus placebo eye drops or corticosteroid eye drops:

The first RCT did not report on harms. In the second RCT, 6/20 (30%) people receiving NSAID eye drops reported a transient stinging sensation in their eyes. In the third RCT, more people receiving indometacin reported eye irritation, although the difference was not significant (7/25 [28%] with indometacin v 3/24 [13%] with dexamethasone; RR 2.2, 95% CI 0.7 to 7.8).

Comment

Two RCTs used 'clinical cure' as an outcome measure, although neither defined this term. The third RCT defined 'clinical cure' as absence of clinical signs or symptoms suggestive of inflammation. The RCT comparing NSAID with placebo eye drops reported that 6/71 (8%) people did not complete the trial, and the second RCT reported that 11/71 (15%) people did not complete the trial. Neither of these RCTs analysed data by intention to treat.

Clinical guide

Decreased vision from photophobia and loss of vision from cystoid macular oedema are the main signs and symptoms that people fear and physicians aim to treat and prevent. Adjunctive oral NSAIDs and cycloplegic eye drops have not yet been evaluated in RCTs.

Substantive changes

No new evidence

BMJ Clin Evid. 2015 May 13;2015:0705.

Mydriatics (different drugs or potencies)

Summary

We found no direct information from RCTs about different mydriatic drugs or different potencies of mydriatic drugs in the treatment of people with acute anterior uveitis.

Benefits

We found no systematic review or RCTs comparing different mydriatic drugs or different potencies of mydriatic drugs for acute anterior uveitis.

Harms

We found no RCTs.

Comment

In this option, we have searched for any mydriatics (e.g., topicamide, cyclopentolate, and atropine).

Clinical guide

Mydriatics are used to prevent posterior synechiae and are widely used to treat photophobia symptoms, despite causing near vision to become blurred.

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

RESOURCES